Inulin as a Carrier for Contrast Agents in Magnetic Resonance Imaging

Magnetic resonance angiography (MRA) has put forth an impetus for the development of macromolecular GdIII complexes that have a prolonged lifetime in the vascular system. Herein, we report the synthesis and GdIII complexation of a new sugar conjugate based on inulin and the DO3A ligand (DO3A=1,4,7,10‐tetraazacyclododecan‐1,4,7‐triacetic acid). Two API‐DO3ASQ conjugates (API=O‐(aminopropyl)inulin, SQ=squaric acid=3,4‐dihydroxy‐3‐cyclobutene‐1,2‐dione) with different degrees of substitution (ds=0.7 and ds=1.5) were prepared from API by using the diethyl ester of squaric acid as a linking agent for the DO3A chelate. The efficacies of the resulting GdIII compounds were evaluated by investigation of their water 1H longitudinal‐relaxation‐rate enhancements at variable field (NMRD). A dramatic increase in relaxivity was observed in the more highly substituted conjugate (ds=1.5); this prompted us to do a variable‐temperature 17O study in order to further characterize the relaxation parameters involved in this system. [Gd(API‐DO3ASQ)] shows promising properties for application as a contrast agent for MRI. A promising new potential contrast agent for MRI, the molecule shown right—a conjugate of the oligosaccharide inulin and the GdIII complex of DO3A—has been synthesized starting from O‐(aminopropyl)inulin with diethyl squarate (3,4‐dihydroxy‐3‐cyclobutane‐1,2‐dione) as a linking agent.